Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genes Dev. 2022;36(21-24):1100-1118. doi: 10.1101/gad.349930.122. Epub 2022 Dec 8.
Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.
神经回路可塑性和感觉反应动力学依赖于形成新的突触连接。尽管最近在理解回路可塑性的后果方面取得了进展，但驱动回路可塑性的机制尚不清楚。嗅球内的成年神经元已被证明是研究回路可塑性的有力模型，为神经元发育、迁移和回路整合提供了广泛而易于进入的途径。我们和其他人已经表明，有效的成年神经元回路整合取决于形式多样的信号肽的突触前活性。在这里，我们展示了一种新的催产素依赖的成年神经元突触成熟和回路整合的机制。我们揭示了在小鼠嗅球中的成年神经元中催产素受体表达的空间和时间富集，其中催产素受体表达在活动依赖性整合期间达到峰值。通过病毒标记、共聚焦显微镜和细胞类型特异性 RNA 测序，我们证明催产素受体信号通过调节新整合的成年神经元的形态发育和成熟突触 AMPAR 和其他结构蛋白的表达，促进其突触成熟。
